Systems and methods for evaluating hemodialysis arteriovenous fistula maturation

ABSTRACT

The invention relates to evaluation of maturity of arteriovenous (AV) fistula using guidewires that measure intravascular blood flow and/or pressure. The invention provides methods of evaluating AV fistula maturation using an instrumented guidewire to measure intravascular flow and/or pressure. By using a small diameter guidewire that does not interfere substantially with the flow, an accurate measurement can be made that is useful for identifying when a fistula is mature and therefore ready to be used for hemodialysis. The flow of blood through the fistula is measured using the guidewire and the measured flow and/or pressure of blood is used to determine if the fistula is mature.

RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 14/596,576 filed Jan. 14, 2015, which claims the benefit of andpriority to U.S. provisional application Ser. No. 61/927,016, filed Jan.14, 2014, the contents of which are incorporated by reference herein intheir entireties.

FIELD OF THE INVENTION

The invention relates to evaluation of maturity of arteriovenous (AV)fistula using guidewires that measure intravascular blood flow and/orpressure.

BACKGROUND

Healthy kidneys remove waste and minerals from the blood. When kidneysfail, harmful waste builds up in the body, blood pressure may rise, andthe body may retain excess fluid and not make enough red blood cells dueto insufficient erythropoietin production. Hemodialysis is a commonmethod for treating kidney failures and involves flowing blood through afilter to remove wastes. For hemodialysis, a fistula is created thatconnects an artery to a vein, or optionally an AV graft is created byusing a tube to connect the artery to the vein. The National KidneyFoundation (NKF), Centers for Medicare and Medicaid Services (CMS),DaVita Patient Citizens (DPC) and other organizations and expertsgenerally agree that fistulas are the best type of vascular access.After creation, a fistula can take several weeks to develop enough to beused, i.e., to reach fistula maturation. Hemodialysis can beunsuccessful or lead to complications if performed before, or too longafter, fistula maturation. The evaluation of maturation by color-flowDoppler ultrasound has been proposed. See, e.g., Toregeani, et al.,2008, Evaluation of hemodialysis arteriovenous fistula maturation bycolor-flow Doppler ultrasound, J Vasc Bras 7(3):203-213 or Ferring, etal., 2008, Vascular ultrasound for the pre-operative evaluation prior toarteriovenous fistula formation for haemodialysis: review of theevidence, Nephrol. Dial. Transplant. 23(6):1809-1815.

Unfortunately, there are drawbacks associated with those procedures. Forexample, where the ultrasound catheter reveals that intravascularintervention is called for, the catheter must be swapped for a catheterthat can perform the intervention (e.g., thrombectomy). Every removaland insertion of a new catheter raises risk of complications.Additionally, even though the ultrasound catheter itself provides someguidance to a treatment location, it does not provide directnavigational guidance for treatment after having been removed from thebody. Further, even though medical organizations recommend fistulaaccess, evaluating maturation is imperfect due to the fact that theultrasound catheter being used to measure flow also partially impedesthat flow. That is, the catheter itself partially occludes flow andinterferes with obtaining an actual measurement of flow through an AVfistula.

SUMMARY

The invention provides methods of evaluating AV fistula maturation usingan instrumented guidewire to measure intravascular blood flow and/orpressure. By using a small diameter guidewire that does not interferesubstantially with the flow, an accurate measurement can be made that isuseful for identifying when a fistula is mature and therefore ready tobe used for hemodialysis. The guidewire can be instrumented to measureflow velocity, pressure, other properties, or a combination thereof. Theguidewire can be operated with a system computer that uses themeasurement to provide information that aids in evaluating maturity.Fistula maturation is correctly identified, allowing hemodialysis to beinitiated at a suitable time, avoiding complications. This lowers costof hemodialysis while improving results, leading to greater patienthealth. Additionally, since the quality of the fistula is evaluated by aguidewire, the same guidewire can be used to guide a catheter to alocation proximal to where the measurement is made. Thus, where theguidewire detects or reveals a need for therapy, the guidewire can beused to guide delivery of the therapy via a catheter, without the needfor a catheter exchange, thus decreasing complications associated withcatheter exchanges.

In certain aspects, the invention provides a method for assessingmaturation of a fistula that includes inserting an instrumentedguidewire into a vessel of a patent. The vessel is in communication witha fistula, which provides fluid communication between the vessel and anadjacent vessel. For example, an arteriovenous fistula for hemodialysismay be assessed. The flow of blood through the fistula is measured usingthe guidewire and the measured flow of blood is used to determine if thefistula is mature. Measuring the flow of blood may include collectingdata with a sensing device on the guidewire while the guidewire iswithin the vessel and relaying the data to a computer. The computerdetermines an observed rate of the flow of blood. Preferably a computerprogram is used to provide information about the maturity of the fistulabased on the observed rate of blood flow. Determining maturation may bedone by comparing the observed rate to a standard. For example, anobserved rate of 600 mL/min or greater may indicate that the fistula ismature. The instrumented guidewire may include an ultrasonic transducer(e.g., for Doppler velocity), a pressure sensor, other sensors, or acombination thereof.

The guidewire may be specially designed for arteriovenous hemodialysisfistula. For example, the guidewire may be shorter than otherintravascular guidewires, stiffer, or both. The guidewire may have adiameter of about 0.035 inches or less. In some embodiments, theguidewire is less than about 110 cm long, and preferably less than about80 cm long (e.g., about 50 to 60 cm long). The guidewire can include astiffening material to give it a desires flexural modulus (e.g., atleast about 15 GPa, or at least about 50 GPa). In some embodiments, theguidewire will have a stiffness of 100 GPa flexural modulus or greater.

In certain embodiments, the method further includes sliding a catheterover the guidewire and using the catheter over the guidewire to delivertherapy to the fistula.

Aspects of the invention provide a system for assessing maturation of afistula. The system includes a sensing guidewire comprising a sensor andconfigured to be inserted into a vessel of a patient and a computercommunicatively linked with the sensing guidewire. The computer receivesa measurement from the sensor and use the measurement to determine anobserved rate of blood flow through a fistula. The system optionally caninclude a catheter to deliver therapy to the fistula. Preferably, thecomputer includes a program in memory that causes the computer toprovide information about the maturity of the fistula based on theobserved rate of blood flow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 diagrams a method of using a guidewire to assess fistulamaturation.

FIG. 2 illustrates a guidewire with a pressure sensor.

FIG. 3 illustrates a guidewire with a flow sensor.

FIG. 4 shows a guidewire tip with a flow sensor and a pressure sensor.

FIG. 5 gives a cross-sectional view through a guidewire tip.

FIG. 6 shows conductors passing through a guide wire.

FIG. 7 illustrates a system of the invention.

DETAILED DESCRIPTION

Methods of the invention use a guidewire with one or more sensor toobtain intraluminal measurements within a body lumen. The sensors arepreferably coupled to signal wires such as electrical conductors, whichrelay signals between the sensors and a workstation. A guidewire of theinvention can include a pressure sensor, a flow sensor, a temperaturesensor or combinations thereof. Preferably, the guidewire is acombination guidewire that includes both a pressure sensor and a flowsensor. Pressure sensors can be used to measure pressure within thelumen and flow sensors can be used to measure the velocity of bloodflow. Temperature sensors can measure the temperature of a lumen. Aguidewire with both a pressure sensor and a flow sensor provides adesirable environment in which to calculate fractional flow reserve(FFR) using pressure readings, and coronary flow reserve (CFR), ornon-coronary vessel flow reserve, using flow readings.

FIG. 1 diagrams a method 101 of using a functional management wire (FMwire) to assess maturation of AV fistulas or grafts. Use of a wireresults in less vessel obstruction than a catheter and offers theability to intervene over the FM wire at the time of the procedure. AnFM wire could provide flow measurements, pressure measurements, others,or a combination thereof.

Functional management is a guide wire based technology that analyzespressure, flow, or both from the inside of a vessel. The wire provides asimple, reproducible measurement, and may be used in conjunction withangiography.

Method 101 starts 105 with a patient with an AV fistula. An instrumentedguidewire is inserted 109 into the appropriate vessel to makemeasurements proximal (e.g., at or near) the AV fistula. In someembodiments, the guidewire is inserted 109 into the vein immediatelydownstream of the fistula. Preferably, measurements are made where flowis laminar. Measurements may be made following generally proceduredescribed in Robbin, et al., 2002, Hemodialysis arteriovenous fistulamaturity: US evaluation, Radiology 225(1):59-64. The flow of bloodthrough the fistula or graft is measured 117.

The observed flow is blood is compared 121 to a standard (e.g., for abinary yes/no call, or to stratify). This can be done using a computerthat receives data from the guidewire. The computer can further provide127 a result supporting a determination of whether the fistula ismature. Any suitable instrumented guidewire can be used to measure 117the blood flow. For example, a functional management guidewire can beused.

FIG. 2 illustrates a guidewire 201 with a pressure sensor 204. Guidewire201 generally defines an elongated body extending from a proximal end210 to a distal end 202. Proximal end 210 connects to connector housing215, which offers a modular plug 221 for connection to a computingdevice in systems of the invention.

A pressure sensor allows one to obtain pressure measurements within abody lumen. A particular benefit of pressure sensors is that pressuresensors allow one to measure of fractional flow reserve (FFR) in vessel,which is a comparison of the pressure within a vessel at positions priorto the fistula and after the fistula. The level of FFR determines thepatency of the fistula, which allows physicians to more accuratelyidentify fistula maturation. For example, an FFR measurement above 0.80may indicate maturation. Another benefit is that a physician can measurethe pressure before and after an intraluminal intervention procedure todetermine the impact of the procedure.

Pressure sensor 204 can be mounted on the distal portion of a flexibleelongate member. In certain embodiments, the pressure sensor ispositioned distal to the compressible and bendable coil segment of theelongate member. This allows the pressure sensor to move away from thelongitudinal axis and coil segment as bended. The pressure sensor can beformed of a crystal semiconductor material having a recess therein andforming a diaphragm bordered by a rim. A reinforcing member is bonded tothe crystal and reinforces the rim of the crystal and has a cavitytherein underlying the diaphragm and exposed to the diaphragm. Aresistor having opposite ends is carried by the crystal and has aportion thereof overlying a portion of the diaphragm. Electricalconductor wires can be connected to opposite ends of the resistor andextend within the flexible elongate member to the proximal portion ofthe flexible elongate member. Additional details of suitable pressuresensors that may be used with devices of the invention are described inU.S. Pat. No. 6,106,476. U.S. Pat. No. 6,106,476 also describes suitablemethods for mounting the pressure sensor 404 within a sensor housing. Asdiscussed above, additionally or alternatively, a guidewire can includea flow sensor. In some embodiments, a guidewire is used that includes aflow sensor. A suitable product for guidewire 201 is the PrimeWirePRESTIGE from Volcano Corporation.

In general, the guide wire of the present invention is comprised of aflexible elongate element having proximal and distal ends and a diameterof 0.018″ and less as disclosed in U.S. Pat. Nos. 5,125,137, 5,163,445,5,174,295, 5,178,159, 5,226,421, 5,240,437 and 6,106,476, all of whichare incorporated by reference herein.

A guidewire of the invention may include a flexible elongate elementhaving proximal and distal extremities, and can be formed of a suitablematerial such as stainless steel, Nitinol, polyimide, PEEK or othermetallic or polymeric materials having an outside diameter for exampleof 0.018″ or less and having a suitable wall thickness, such as, e.g.,0.001″ to 0.002″. This flexible elongate element is conventionallycalled a hypotube. In one embodiment, the hypotube may have a length ofless than 120 cm, preferably about 50, 60, 70, or 80 cm. Typically, sucha guide wire may further include a stainless steel core wire extendingfrom the proximal extremity to the distal extremity of the flexibleelongate element to provide the desired torsional properties tofacilitate steering of the guide wire in the vessel and to providestrength to the guidewire and prevent kinking.

In a preferred embodiment, methods of the invention employ a guidewirewith improved stiffness, relative to prior art guidewires. For example,the guidewire can include a stiffening material such as a stainlesssteel core or a less pliable plastic (e.g., less pliable than Nitinol,polyimide, or PEEK). Preferably, the guidewire has a flexural modulus ofat least 15 GPa. In some embodiments, the guidewire has a flexuralmodulus of at least 50 GPa (e.g., as measured and described in Harrisonet al., 2011, What's in a name?, J Endo Ther 18(6):797-801). Forexample, the guidewire may be made with the stiffness of an Amplatz typesuper-stiff or ultra-stiff guidewire. The guidewire can have a diameterof about 0.014″ (0.35 mm) and can include the functional instrumentationof the Doppler guide wire sold under the name FLOWIRE by VolcanoCorporation, the pressure guidewire sold under the name PRIMEWIREPRESTIGE by Volcano Corporation, or both.

FIG. 3 illustrates a guidewire 201 with a flow sensor 305. The flowsensor can be used to measure blood flow velocity within the vessel,which can be used to assess coronary flow reserve (CFR), or similar. Theflow sensor can be, for example, an ultrasound transducer, a Dopplerflow sensor or any other suitable flow sensor, disposed at or in closeproximity to the distal tip of the guidewire. The ultrasound transducermay be any suitable transducer, and may be mounted in the distal endusing any conventional method, including the manner described in U.S.Pat. Nos. 5,125,137, 6,551,250 and 5,873,835. A suitable product forguidewire 201 with a flow sensor 305 is the FLOWIRE from VolcanoCorporation.

In a preferred embodiment, methods of the invention employ a guidewirethat includes a device for measuring pressure and a device for measuringflow. For example, in use, the guidewire may be advanced to a fistula.The pressure and flow velocity may then be measured.

The ability to take the pressure and flow measurements at the samelocation and same time with the combination tip sensor, improves theaccuracy of the diagnostic information.

FIG. 4 shows a combination sensor tip 400 of a guidewire 201 accordingto embodiments of the present invention. The combination sensor tip 400includes a pressure sensor 404 within sensor housing 403, and optionallyincludes a radiopaque tip coil 405 distal to proximal coil 406.

FIG. 5 gives a cross-sectional view through combination sensor tip 400,showing ultrasound transducer 501 disposed therein. The ultrasoundtransducer 501 may be any suitable transducer, and may be mounted in thedistal end using any conventional method, including the manner describedin U.S. Pat. No. 5,125,137, which is fully incorporated herein byreference. Conductors (not shown) may be secured to the front and rearsides of the ultrasound transducer 501, and the conductors may extendinteriorly to the proximal extremity of a guide wire.

The combination sensor tip 400 also includes a pressure sensor 404 alsodisposed at or in close proximity to the distal end 202 of thecombination sensor tip 400. The pressure sensor 404 may be of the typedescribed in U.S. Pat. No. 6,106,476, which is fully incorporated hereinby reference. For example, the pressure sensor 404 may be comprised of acrystal semiconductor material having a recess therein and forming adiaphragm bordered by a rim. A reinforcing member may be bonded to thecrystal to reinforce the rim of the crystal, and may have a cavitytherein underlying the diaphragm and exposed to the diaphragm. Aresistor having opposite ends may be carried by the crystal and may havea portion thereof overlying a portion of the diaphragm. Leads may beconnected to opposite ends of the resistor and extend proximally withinthe guide wire. Additional details of suitable pressure sensors that maybe used as the pressure sensor 404 are described in U.S. Pat. No.6,106,476. U.S. Pat. No. 6,106,476 also describes suitable methods formounting the pressure sensor 404 within the combination sensor tip 400.In one embodiment, the pressure sensor 404 is oriented in a cantileveredposition within a sensor housing 403. For example, the sensor housing403 preferably includes a lumen surrounded by housing walls. When in acantilevered position, the pressure sensor 404 projects into the lumenof the sensor housing 403 without contacting the walls of the sensorhousing 403.

In FIG. 5, ultrasound transducer 501 is illustrated as disposed neardistal end 202. One advantage of the sensor housing 403 is that becausethe sensor housing 403 encloses both the ultrasound transducer 501 andthe pressure sensor 404, the need for two separate housings, i.e., onefor an ultrasound transducer and one for a pressure sensor, iseliminated. Accordingly, the use of a common sensor housing 403 for theultrasound transducer 501 and the pressure sensor 404 makes thecombination sensor tip 400 easier to manufacture than current designs.

Additionally, the combination sensor tip 400 of the present inventionprovides for both the ultrasound transducer 501 and the pressure sensor404 to be disposed near the distal end of the combination sensor tip400. The combination sensor tip 400 of the present invention isadvantageous because by having both the ultrasound transducer 501 andthe pressure sensor 404 near its distal end, the combination sensor tip400 is capable of being positioned distally beyond the fistula.Additionally, the combination sensor tip 400 of the present invention,unlike the prior art, is also able to take measurements from theultrasound transducer 501 and the pressure 104 at approximately the samelocation and approximately the same time, thereby resulting in greaterconsistency of measurements, greater accuracy of measurements, andgreater accuracy of placement within the body. Furthermore, placement ofboth the ultrasound transducer 501 and the pressure sensor 404 near thedistal end of the combination sensor tip 400 increases overallflexibility in a guide wire that incorporates the combination sensor tip400. For example, a prior art guide wire that includes separate sensors,with the pressure sensor being located substantially proximal from theultrasound transducer, has a longer relatively rigid area that must bedevoted to the pressure and flow sensors, i.e., the distance from theultrasound transducer to the pressure sensor. The present invention, incontrast, substantially reduces or entirely eliminates the distancebetween the ultrasound transducer and the pressure sensor, therebyallowing for increased flexibility across this length.

It should be noted that in an alternative embodiment of the combinationsensor tip 400 (not shown) both the ultrasound transducer 501 and thepressure sensor 404 may be offset from the distal end of the combinationsensor tip 400, such as, e.g., 1.5 cm to 3.0 cm from the distal end, butstill located in close proximity to each other relative to prior artdesigns. Thus, the aforementioned advantages over the prior art designare still achieved.

In an alternative embodiment, the pressure sensor housing includes atubular member having an opening on the outer wall in communication withthe lumen and a tip. The tip is constructed of a solder ball.Alternatively, a weld, braze, epoxy or adhesive can be used. The lumenof the housing is counter-bored so that the lumen has a smaller innerdiameter at the proximal end of the tubular member. For example, thehousing may be constructed in the counter-bore fashion with a 0.010″inner diameter at the proximal end and a 0.012″ inner diameter at thedistal end, with the pressure transducer coaxially housed in the lumen.In addition, a flow sensor may be placed in the sensor tip instead ofthe weld, braze, epoxy or adhesive to provide a combo sensor tip. Theadvantage of the counter bore is that the housing is easier to make. Thetransducer is simply slid into place in the lumen and bonded (adhesiveor epoxy) where the sides meet the proximal 0.010″ inner diameter 314.The distal 0.012″ inner diameter allows enough room for the pressuresensitive section of the transducer to be free from any contact with thehousing. Because of the counter-bored lumen, there is no ledge that hasto be made on the outer wall of the lumen, rather the pressuretransducer communicates with the outside via an opening in the outerwall of lumen. Constructions suitable for use with a guidewire of theinvention are discussed in U.S. Pub. 2013/0030303 to Ahmed, the contentsof which are incorporated by reference.

A radiopaque tip coil 405 may be provided at the proximal end of thecombination sensor tip 400. The radiopaque tip coil 405 is coupled to aproximal coil 106, and the proximal coil 106 may be coupled to theelongate tubular member. Another improvement of the present inventionover current designs that use separate pressure sensor and ultrasoundtransducer housings is that the present invention provides a smoothertransition from the elongate tubular member to the combination sensortip 400, i.e., the connection between the radiopaque tip coil 405, theproximal coil 106, and the rest of the guide wire is optimized relativeto current designs. Specifically, the transition is smoother and moreflexible because of the absence of the housing between the radiopaquetip coil 405 and the proximal coil 106. Current designs generally have atip coil 5 attached to a pressure sensor housing 3, which in turn isconnected to a proximal coil 6. The present invention eliminates orgreatly reduces the separation between the tip coil and the proximalcoil that is required in current devices. Suitable coils for use withthe present invention are described in U.S. Pat. No. 6,106,476.

FIG. 6 shows fine wire conductors 607 passing through the guide wire toconductive bands 608 near the proximal end 210 of the guide wire.Signals from the ultrasound transducer 501 and the pressure sensor 404may be carried by conductors 607. Usually three electrical connectorsare necessary for a stand-alone pressure measurement guidewire and twoelectrical connectors are necessary for a stand-alone flow measurementguidewire. Thus, a guide wire incorporating the combination sensor tip400 of the present invention includes five electrical conductors 607extending through the lumen of the guidewire and five conductive bands608 on the proximal end 610 of the guidewire. The conductive bands 608may be electrically isolated from each other by means of epoxy 609.Alternatively, polyimide tubes may be used to isolate conductors fromthe conductive bands.

The electrical connection wires can include a conductive core made froma conductive material, such as copper, and an insulating coating, suchas a polyimide, Fluoro-polymer, or other insulating material. Theelectrical connection wires extend from one or more sensors located onthe distal end of the guidewire, run down the length of the guidewire,and connect to a connector housing at a proximal end.

Any suitable arrangement of the electrical connection wires through thelength of the elongate member can be used. The arrangement of electricalconnection wires must provide for a stable connection from the proximalend of the guidewire to the distal end of the guidewires. In addition,the electrical connection wires must be flexible and/or have enoughslack to bend and/or move with the adjustable distal portion withoutdisrupting the sensor connection. In one embodiment, the electricalconnections run next the core member within the lumen of the elongatemember.

In yet another embodiment, the electrical connector wires 707 arewrapped around a core member of the guidewire and then covered with apolyimide layer. At a distal end of the core member near the sensors,the polyimide layer can be dissected away, which frees the wires toextend and connect to their respective sensors. The length of theelectrical connector wire running free from the core member andconnected to the sensor should have enough slack/flexibility to remainconnected to the sensor during bending of the guidewire.

Preferably, proximal end 610 connects to connector housing 215 as shownin FIG. 2. In certain embodiments, the electrical connector wires arejoined together to form a male connector at a proximal end. The maleconnector mates with a female connector of the connector housing. Thetermination of the male connector can be performed by a metal depositionprocess as described in U.S. Pat. No. 6,210,339, incorporated herein byreference in its entirety. The deposited metal (or any conductivematerial) permanently adheres or couples to the exposed conductive wiresat points where the polyimide layers were removed. After the maskingmaterial is removed, there are independent conductive stripes, eachconnected to a different respective electric wire. Because of theprecision nature of the winding process as well as the masking and metaldeposition processes, a male connector is made that is short in length,yet very reliable, in mating with a female connector and cable.Alternatively, conductive bands may be coupled to the exposed ends ofthe electric wires instead of the metallizing process.

The connector housing can be connected to an instrument, such as acomputing device (e.g. a laptop, desktop, or tablet computer) or aphysiology monitor that converts the signals received by the sensorsinto pressure and velocity readings in systems of the invention.

In advanced embodiments, the systems of the invention incorporatefocused acoustic computed tomography (FACT), which is described inWO2014/109879, incorporated herein by reference in its entirety.

FIG. 7 illustrates a system 701 of the invention. System 701 includes aninstrumented guidewire 201 operably coupled to a computer device 705.Guidewire 201 includes at least one sensor such as a pressure sensor orflow sensor as discussed above. Guidewire 201 may include a plurality ofsensor such as a pressure sensor and a flow sensor as discussed above.Computer 705 can be a dedicated medical imaging instrument, a standarddesktop, laptop, or tablet computer, or a combination thereof (e.g., amedical imaging instrument with a base station and a laptop or desktopcomputer attached to provide a workstation and interface for aphysician. Computer 705 can receive a measurement from the sensor onguidewire 201 and use the measurement to determine an observed rate ofblood flow through a fistula. In some embodiments, computer 705 comparesthe observed rate of a blood flow to a standard or an expected rate ofblood flow to provide an aid in assessing fistula maturation. Forexample, computer 705 may have a software program in memory that storesa standard (e.g., 600 mL/min) flow rate. By making a comparison, if aflow rate is sub-standard, the fistula can be deemed to be not mature.If the flow rate meets the standard, the fistula may be deemed mature.The instrument can further calculate Coronary Flow Reserve (CFR)—orsimilar—and Fractional Flow Reserve (FFR) and provide the readings andcalculations to a user via a user interface.

In some embodiments, a user interacts with a visual interface to viewimages from the imaging system. Input from a user (e.g., parameters or aselection) are received by a computer device or processing instrument.Electrical signals are relayed from the conductors via a matingconnector (or contact housing as described herein with respect to aconnector of the present invention) to an instrument, such as, e.g., aphysiology monitor, that converts the signals into pressure and velocityreadings that are displayed to the user. In addition, algorithms such asCoronary Flow Reserve (CFR)—or similar—and Fractional Flow Reserve (FFR)are calculated.

System 701 may include one or a plurality of computer. For example,system 701 may include computer 705 as a bed-side workstation or in acontrol room and system 701 may additionally include a server computerfor processing measurements or for receiving measurements from aplurality of Cath labs. A computer in system 701 such as computer 705generally includes a processor coupled to memory and one or moreinput/output devices. Computer 705 may be provided by a desktopcomputer, laptop, tablet, mobile device, or purpose-built machine (suchas a bed-side control station for a medical imaging system).

A processor generally refers to a computer microchip such as theprocessor sold under the trademark CORE 17 by Intel (Santa Clara,Calif.).

Memory generally includes one or more devices for random access,storage, or both. Preferably, memory includes a tangible, non-transitorycomputer readable medium, and may be provided by one or more of a solidstate drive (SSD), a magnetic disc drive (aka, “a hard drive”), flashmemory, an optical drive, others, or a combination thereof.

An I/O device may include one or more of a monitor, keyboard, mouse,touchscreen, Wi-Fi card, cell antenna, Ethernet port, USB port, light,accelerometer, speaker, microphone, drive for removable disc, others, ora combination thereof. Preferably, any combination of computer in system701 may communicate through the use of a network, which may includecommunication devices for internet communication, telephoniccommunication, others, or a combination thereof.

As will be appreciated from the above, the invention provides systemsand methods for evaluating the maturation of arteriovenous (AV) fistulausing an instrumented guidewire that measures intravascular flow and/orpressure (an FM wire). By using a small diameter guidewire that does notinterfere substantially with the flow, an accurate measurement can bemade that is useful for identifying when a fistula is mature andtherefore ready to be used for hemodialysis. The flow of blood throughthe fistula is measured using the guidewire and the measured flow ofblood is used to determine if the fistula is mature. Preferably, theguidewire has a flexural modulus of at least 15 GPa and preferably atleast 50 GPa. The guidewire may be made with the stiffness of an Amplatztype super-stiff or ultra-stiff guidewire. The guidewire can have adiameter of about 0.014″ (0.35 mm) to 0.035″ (0.89 mm). The guidewiremay have length of less than 120 cm (e.g., about 80 cm). The guidewiresmay be provided in a system that includes a computer (that includes aprocessor coupled to a tangible, non-transitory memory) that analyzesflow measurements to evaluate fistula maturation (e.g., comparing themeasured flow to a standard). The standard may be 600 mL/min and thecomputer can aid the determination that flow that meets or exceeds thestandard indicates fistula maturation.

INCORPORATION BY REFERENCE

References and citations to other documents, such as patents, patentapplications, patent publications, journals, books, papers, webcontents, have been made throughout this disclosure. All such documentsare hereby incorporated herein by reference in their entirety for allpurposes.

EQUIVALENTS

Various modifications of the invention and many further embodimentsthereof, in addition to those shown and described herein, will becomeapparent to those skilled in the art from the full contents of thisdocument, including references to the scientific and patent literaturecited herein. The subject matter herein contains important information,exemplification and guidance that can be adapted to the practice of thisinvention in its various embodiments and equivalents thereof.

What is claimed is:
 1. A tangible, non-transient computer readable medium comprising microprocessor executable instructions that, when executed, perform operations comprising: receiving, from a flow sensor, a first flow rate measurement of blood through a fistula in fluid communication with a vessel; receiving, from a pressure sensor, a first pressure measurement of blood adjacent the fistula; determining, using the first flow rate measurement and the first pressure measurement, whether a therapy to the fistula is indicated; providing a result indicative of a need to apply therapy to the fistula; after determining whether the therapy to the fistula is indicated, receiving a second flow rate measurement of blood through the fistula and a second pressure measurement of blood adjacent the fistula; and determining, using the second flow rate measurement and the second pressure measurement, whether further therapy to the fistula is indicated.
 2. The tangible, non-transient computer readable medium of claim 1, wherein the microprocessor executable instruction(s) for determining, using the first flow rate measurement and the first pressure measurement, whether a therapy to the fistula is indicated comprises comparing the first flow rate measurement to a predetermined flow rate.
 3. The tangible, non-transient computer readable medium of claim 2, whereupon the first flow rate measurement equal equal to or greater than the predetermined flow rate, the therapy is indicated.
 4. The tangible, non-transient computer readable medium of claim 3, wherein the predetermined flow rate is 600 mL/min.
 5. The tangible, non-transient computer readable medium of claim 1, wherein the microprocessor executable instruction(s) for determining, using the first flow rate measurement and the first pressure measurement, whether a therapy to the fistula is indicated comprises determining whether the fistula is mature.
 6. The tangible, non-transient computer readable medium of claim 1, wherein the microprocessor executable instruction(s) for determining, using the first flow rate measurement and the first pressure measurement, whether a therapy to the fistula is indicated comprises determining a level of maturation of the fistula.
 7. The tangible, non-transient computer readable medium of claim 6, wherein determining the level of maturation of the fistula is based upon whether the first flow rate measurement is equal to or greater than a predetermined flow rate.
 8. The tangible, non-transient computer readable medium of claim 7, wherein the predetermined flow rate of blood is 600 mL/min.
 9. The tangible, non-transient computer readable medium of claim 6, wherein determining the level of maturation of the fistula is based upon whether the first pressure measurement is greater than a predetermined pressure.
 10. The tangible, non-transient computer readable medium of claim 9, wherein the first pressure measurement is indicative of a fractional flow reserve.
 11. The tangible, non-transient computer readable medium of claim 10, wherein the predetermined pressure is 0.80.
 12. The tangible, non-transient computer readable medium of claim 7, wherein determining a level of maturation of the fistula is based upon whether the first pressure measurement is greater than a predetermined pressure.
 13. The tangible, non-transient computer readable medium of claim 12, wherein the first pressure measurement is indicative of a fractional flow reserve.
 14. The tangible, non-transient computer readable medium of claim 13, wherein the predetermined pressure is 0.80.
 15. The tangible, non-transient computer readable medium of claim 1, wherein the microprocessor executable instruction(s) for determining, using the first flow rate measurement and the first pressure measurement, whether a therapy to the fistula is indicated comprises comparing the first pressure measurement to a predetermined pressure.
 16. The tangible, non-transient computer readable medium of claim 15, whereupon the first pressure measurement being greater than the predetermined pressure, the therapy is indicated.
 17. The tangible, non-transient computer readable medium of claim 16, wherein the predetermined pressure is 0.80.
 18. A system for assessing a fistula, the system comprising: a guidewire comprising a flow sensor and a pressure sensor; and a computer communicatively coupled to the guidewire, wherein the computer comprises a memory and executable instructions stored in the memory, whereupon being executed, the executable instructions perform operations comprising: receiving, from the flow sensor, a first flow rate measurement of blood through a fistula in fluid communication with a vessel; receiving, from the pressure sensor, a first pressure measurement of blood adjacent the fistula; determining, using the first flow rate measurement and the first pressure measurement, whether a therapy to the fistula is indicated; providing a result indicative of a need to apply therapy to the fistula; receiving a second flow rate measurement of blood through the fistula and a second pressure measurement of blood adjacent the fistula; and determining, using the second flow rate measurement and the second pressure measurement, whether further therapy to the fistula is indicated.
 19. The system of claim 18, wherein the microprocessor executable instruction(s) for determining, using the first flow rate measurement and the first pressure measurement, whether the therapy to the fistula is indicated comprises comparing the first flow rate measurement to a predetermined flow rate and comparing the first pressure measurement to a predetermined pressure.
 20. The system of claim 19, whereupon the first flow rate measurement being equal to or greater than the predetermined flow rate and the first pressure measurement being equal greater than the predetermined pressure, the therapy is indicated. 